1. Field of the Invention
The present invention is directed to a method of treating presenile or senile dementia and to the discovery that a mammalian liver extract that is efficacious in treating such diseases. The present invention is also directed to a method of treating such diseases with this same mammalian liver extract and/or with polypeptides shown in Sequence identification numbers 1-9.
2. Description of the Prior Art
Presenile or senile dementias include Alzheimer's disease, cerebrovascular amyloidosis, dementia associated with Down's Syndrome and Familial Icelandic cerebrovascular amyloidosis.
Alzheimer's disease is the most common form of dementia. About 70% of all cases of dementia are due to Alzheimer's disease. Alzheimer's disease is characterized by memory loss associated with neuronal degeneration in the hippocampus, generation of amyloid plaques in many areas of grey matter, death of neurons with formation of abnormal cytoskeletal structures, and profound cholinergic deficiency. Goldman et al., Aging of the Brain: Dementia of the Alzheimer's Type chapter 62, Part x. Development, Critical Periods, and the Emergence of Behavior, 976, 982 (1991). Symptoms of Alzheimer's Disease include a gradual memory loss, decline in ability to perform routine tasks, impairment of judgment, disorientation, personality change, difficulty in learning, and loss of language skills. A progressive, degenerative disease, it eventually renders victims totally incapable of caring for themselves. More than three million Americans are afflicted with Alzheimer's Disease--one in six over the age of sixty-five. After heart disease, cancer, and stroke, it is the fourth leading cause of death in adults.
Mammalian liver extract has been used for the treatment of a wide range of infectious and noninfectious dermatologic conditions, including acne vulgaris, Journal Invest Dermatology, 2:205-218 (1939); first and second degree burns, Mississippi Valley Medical Journey, 76:199 (1954); sunburn, Clinical Medicine, 3:245 (1956); poison ivy dermatitis, Clin. Med., 3:425 (1956) and Herpes zoster, Southern Medical Journal, 50:1524 (1957). The active principle and mechanism have not been described. Although some medical practitioners have used liver extract for the treatment of dermatologic conditions, it is not regarded as an antiviral or immune modulator agent even for skin therapy.
Mammalian liver extract has been reported to have bradykinin potentiating activity. Tewksbury et al., Arch. Biochem. Biophys. (U.S.). 112, 453 (1965); Tewksbury, Archives Int'l. de Pharmacodynamie et de Therapie, 173, 426 (1968); Tewksbury, Dissertation Abstracts International-Part II, Vol. 25/04, p. 2214 (1964). Further, one commercially-available liver extract (sold under the trademark KUTAPRESSIN by Kremers-Urban Co., Milwaukee, Wis.) exerts its action, according to product literature, only with respect to tissues that have been injured and when inflammation and edema are present.
In related patent 5,055,296, the use of a heat stable acetone-insoluble, water-soluble mammalian liver extract was shown to be effective in the treatment of mammals infected with nondermatologic viruses, in particular, in the treatment of chronic fatigue syndrome. It has been observed that the clinical symptomatology of chronic fatigue syndrome sometimes resembles a mild form of nonprogressive acquired Alzheimer-like disease. Thus, with this background, the inventors endeavored to discover a method to treat presenile or senile dementia diseases.